Hopes for developing effective treatments for Alzheimer disease (AD) rest on clinical research, which will, by necessity, need to enroll AD patients, many of whom lack capacity to consent to research. AD researchers therefore must often rely on proxy consent alongside patient assent. The ethical integrity of AD research is thus highly dependent on proxy consent. Yet, very little is known about what factors influence proxies'decisions about enrolling their relatives, how proxies evaluate risks and benefits, and what factors influence their understanding of research protocols. This proposed work pertains to a focused, yet critical question: how do proxies make decisions about protocols of varying risk and benefit levels? Few empirical studies have used systematically varied, realistic protocols as stimuli to study proxy decision making. By carefully controlling the stimulus protocols and measuring a variety of potential influences on proxy decision making, we will provide important empirically grounded information regarding proxy consent. We will randomly assign 200 AD proxy decision makers to receive consent for one of four hypothetical AD pharmacologic research protocols, systematically varied by level of potential risk and potential for direct patient benefit. Aims include: (1) to determine influences on proxies'research decisions and perceptions of AD research, including perceived risks and benefits;and (2) to examine potential influences on the decision making abilities of the proxies themselves. In addition, we will evaluate several exploratory aims, including: examining an array of potential influences on proxies'willingness to enroll their relative and their perceptions of protocol risks and benefits, including the possible roles of caregiver burden and depression, patient illness severity, proxy/patient relationship, gender, and ethnicity;studying concordance between expert-defined levels of risk and benefit and proxies'perceptions;and exploring how proxies conceptualize the decision-making task as well as how proxies feel about serving as decision makers. Both scalar and open-ended questions will be used to generate a rich dataset focused on developing a nuanced contextual framework for understanding proxy decision making. This research has high public health and bioethical significance, as it will address issues that are fundamental to ethical enrollment of AD patients in vital clinical research, but for which little empirical data currently exist to guide research practice or policy.